Based on a large body of evidence, vitamin D has emerged as a potential determinant of type 2 diabetes (t2DM) risk. In longitudinal observational studies, higher vitamin D status was associated with up to 83% reduction in the risk of t2DM. However, the evidence to support vitamin D supplementation for prevention of t2DM remains inconclusive. The favorable association between vitamin D status and t2DM risk in observational studies may be confounded by a variety of factors, and long-term, well-designed and adequately powered trials are lacking. The ?Vitamin D and type 2 diabetes? (D2d) study is being funded by NIH to provide definitive conclusions regarding the role of vitamin D supplementation for prevention of t2DM. D2d is an ongoing, multicenter, randomized (1:1), double-masked, placebo-controlled, parallel-group, primary prevention clinical trial with two groups (oral 4,000 IU/day of vitamin D3 vs. placebo) among participants at risk for diabetes who are followed for incident diabetes. D2d is designed as an event-driven trial. The study met its enrollment goal in December 2016 and 98% of enrolled participants continue in D2d after a mean follow-up of 19 months. Adherence to study pills is very high (>92% of pills prescribed). The primary aim of the renewal grant is to continue follow- up of the D2d population (N=2,423) and complete the study according to the protocol, which has been approved by the DSMB and all participating IRBs, to answer the study?s primary question: does oral daily vitamin D3 supplementation lower risk of incident diabetes among U.S. adults at high risk for diabetes? Secondary Aims will assess: the heterogeneity of treatment effect of vitamin D supplementation on incident diabetes in subgroups defined by key baseline characteristics (e.g., blood 25-hydroxyvitamin D concentration), effects on secondary outcomes (e.g., blood pressure), and the long-term safety and tolerability of 4000 IU/day of vitamin D3 supplementation. Finally, data from the D2d placebo group will define the natural history of pre- diabetes using the new American Diabetes Association diagnostic criteria that include hemoglobin A1c. The need for a trial such as the D2d study has been recognized in multiple editorials and reviews, including the 2011 Institute of Medicine report on dietary reference intakes for vitamin D, which identified diabetes as one of the most promising non-skeletal outcomes with an urgent need for rigorously conducted trials to confirm the promising results seen in observational and mechanistic studies.